Cognitive impairment occurs in a large percent of lupus patients. We have recently shown that a subset of anti-DNA antibodies in patients with SLE binds to a defined linear epitope on the NR2 NMDA receptor. These antibodies can be found in the cerebrospinal fluid (CSF) as well as in serum. We initially, proposed to explore further the antigenicity of the NR2 receptor in SLE and the functional consequence,' of anti-receptor antibodies in a mouse model of disease. We have now acquired sufficient data from murine studies to show that cognitive impairment can be mediated by these antibodies and is associated with alterations in magnetic resonance spectroscopy. We, therefore, propose a new aim to this study: to determine if there is an association of anti-NR2 antibody, abnormal magnetic resonance spectroscopy and impaired cognitive function in a cohort of 30 SLE patients. In a longitudinal study, we will evaluate whether changes in cognitive performance are accompanied spectroscopic changes. The overall goal of this pilot study is to generate the data to design a definitive study. Ultimately, we hope to develop the scientific foundation for a clinical trial of NR2 receptor antagonists to protect against cognitive decline in SLE. [unreadable] [unreadable]